Real-Time Multi-Photon Tracking and Bioimaging of Glycosylated Theranostic Prodrugs upon Specific Enzyme Triggered Release

Elena Calatrava-Pérez; Luke A. Marchetti; Gavin J. McManus; Dylan M. Lynch; Robert B. P. Elmes; D. Clive Williams; Thorfinnur Gunnlaugsson; Eoin M. Scanlan

doi:10.1002/chem.202103858

Real-Time Multi-Photon Tracking and Bioimaging of Glycosylated Theranostic Prodrugs upon Specific Enzyme Triggered Release

Elena Calatrava-Pérez
, Luke A. Marchetti
, Gavin J. McManus
, Dylan M. Lynch
, Robert B. P. Elmes
, D. Clive Williams
, Thorfinnur Gunnlaugsson (Lead / Corresponding author)
, Eoin M. Scanlan (Lead / Corresponding author)

Biological Chemistry and Drug Discovery

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

Real-time tracking of prodrug uptake, delivery and activation in vivo represents a major challenge for prodrug development. Herein, we demonstrate the use of novel glycosylated theranostics of the cancer pharmacophore Amonafide in highly-selective, enzymatic triggered release. We show that the use of endogenous enzymes for activated release of the therapeutic component can be observed, in real time, and monitored using one and two-photon bioimaging, offering unique insight into the prodrug pharmacokinetic profile. Furthermore, we demonstrate that the potent cytotoxicity of Amonafide is preserved using this targeted approach.

Original language	English
Article number	e202103858
Number of pages	7
Journal	Chemistry - A European Journal
Volume	28
Issue number	3
Early online date	24 Nov 2021
DOIs	https://doi.org/10.1002/chem.202103858
Publication status	Published - 13 Jan 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

antitumor agents
carbohydrates
glycosidase
imaging agents
prodrugs

ASJC Scopus subject areas

Catalysis
Organic Chemistry

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10.1002/chem.202103858

Cite this

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title = "Real-Time Multi-Photon Tracking and Bioimaging of Glycosylated Theranostic Prodrugs upon Specific Enzyme Triggered Release",

abstract = "Real-time tracking of prodrug uptake, delivery and activation in vivo represents a major challenge for prodrug development. Herein, we demonstrate the use of novel glycosylated theranostics of the cancer pharmacophore Amonafide in highly-selective, enzymatic triggered release. We show that the use of endogenous enzymes for activated release of the therapeutic component can be observed, in real time, and monitored using one and two-photon bioimaging, offering unique insight into the prodrug pharmacokinetic profile. Furthermore, we demonstrate that the potent cytotoxicity of Amonafide is preserved using this targeted approach.",

keywords = "antitumor agents, carbohydrates, glycosidase, imaging agents, prodrugs",

author = "Elena Calatrava-P{\'e}rez and Marchetti, \{Luke A.\} and McManus, \{Gavin J.\} and Lynch, \{Dylan M.\} and Elmes, \{Robert B. P.\} and Williams, \{D. Clive\} and Thorfinnur Gunnlaugsson and Scanlan, \{Eoin M.\}",

note = "Funding Information: This work was supported by Science Foundation Ireland (SFI) under grant number 13/IA/1865. Publisher Copyright: {\textcopyright} 2021 Wiley-VCH GmbH",

year = "2022",

month = jan,

day = "13",

doi = "10.1002/chem.202103858",

language = "English",

volume = "28",

journal = "Chemistry - A European Journal",

issn = "0947-6539",

publisher = "Wiley",

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}

TY - JOUR

T1 - Real-Time Multi-Photon Tracking and Bioimaging of Glycosylated Theranostic Prodrugs upon Specific Enzyme Triggered Release

AU - Calatrava-Pérez, Elena

AU - Marchetti, Luke A.

AU - McManus, Gavin J.

AU - Lynch, Dylan M.

AU - Elmes, Robert B. P.

AU - Williams, D. Clive

AU - Gunnlaugsson, Thorfinnur

AU - Scanlan, Eoin M.

PY - 2022/1/13

Y1 - 2022/1/13

N2 - Real-time tracking of prodrug uptake, delivery and activation in vivo represents a major challenge for prodrug development. Herein, we demonstrate the use of novel glycosylated theranostics of the cancer pharmacophore Amonafide in highly-selective, enzymatic triggered release. We show that the use of endogenous enzymes for activated release of the therapeutic component can be observed, in real time, and monitored using one and two-photon bioimaging, offering unique insight into the prodrug pharmacokinetic profile. Furthermore, we demonstrate that the potent cytotoxicity of Amonafide is preserved using this targeted approach.

AB - Real-time tracking of prodrug uptake, delivery and activation in vivo represents a major challenge for prodrug development. Herein, we demonstrate the use of novel glycosylated theranostics of the cancer pharmacophore Amonafide in highly-selective, enzymatic triggered release. We show that the use of endogenous enzymes for activated release of the therapeutic component can be observed, in real time, and monitored using one and two-photon bioimaging, offering unique insight into the prodrug pharmacokinetic profile. Furthermore, we demonstrate that the potent cytotoxicity of Amonafide is preserved using this targeted approach.

KW - antitumor agents

KW - carbohydrates

KW - glycosidase

KW - imaging agents

KW - prodrugs

UR - https://www.scopus.com/pages/publications/85120620951

U2 - 10.1002/chem.202103858

DO - 10.1002/chem.202103858

M3 - Article

C2 - 34820925

AN - SCOPUS:85120620951

SN - 0947-6539

VL - 28

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 3

M1 - e202103858

ER -

Real-Time Multi-Photon Tracking and Bioimaging of Glycosylated Theranostic Prodrugs upon Specific Enzyme Triggered Release

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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